Halogen derivatives of alpha-methylbutyl cresols



Patented July 6, 1937 UNITED STATES PATENT OFFICE HALOGEN DERIVATIVES F a-METHYL- BUTYLICRESOLS linois No Drawing. Application June 22, 1934,

r Serial No. 731,896

6 Claims.

Our invention relates to new halogen derivatives of a-methyLbutyl cresols, which derivatives we have prepared and have been found by us to possess surprisingly high germicidal values and low toxicities, the germicidal power thereof exceeding the corresponding non-halogen compounds. Our new compounds are of considerable value to the medicalprofession as bactericidal and bacteriostatic agents.

10 The compounds described below, all of which we have prepared, include monochloro, dichloro, monobromo, and dibromo derivatives of the amethyl-butyl cresols. The unhalogenated alkyl cresols herein referred to may be prepared as described in our co-pending application, Serial No. 731,898, filed June 22, 1934.

Briefly, this method comprises heating the particular alcohol with zinc chloride to the specific reaction temperature and then slowly adding the desired cresol; maintaining the reaction temperature until the reaction is complete and then pouring the mixture into acidified water. The

alkylated cresol which separates is washed with.

water and extracted with alkali, the alkaline extract in turn being extracted with petroleum ether. The alkyl cresol is separated from its alkaline solution by acidifying with HCl, the desired product being again washed and distilled in vacuo. EXAMPLE 1 Monochloro (u-methyl-butyl) Who-cresol om-om-Crc-ch- 0] 27 grams of sulfuryl chloride are added slowly to 36 grams of (u-methyl-butyl) ortho-cresol in a flask fitted with a dropping funnel and reflux condenser. Warming on a water bath is sometimes necessary to start the reaction." After the is no further evolution of hydrogen chloride or addition of the chloride is complete and there ether solution is dried over sodium sulphate, filtered, the ether distilled off, and the residue distilled under vacuum. I

The monochloro (u-methyl-butyl) ortho-cresol boils at 142-150 C. at 10 mm. pressure and has a specific gravity of 1.059. It is a colorless oil, insoluble in water, soluble in organic solvents and dilute alkali.

EXAMPLE 2 Mo'nochloro (a-methyl -butyl) meta-cresol 10 CHI cavern-carer:

This compound is prepared in exactly the same manner as the previous compound, substituting 20 (a-methyl-butyl) meta-cresol for the ortho derivative. This compound boils at 145 150 C. at 15 mm. pressure and has a specific gravity of 1.142.

It is a colorless oil, insoluble in Water, soluble in organic solvents and dilute alkali. 25

EXAMPLE 3 Monochlorc (a-methyl-butyl) para-cresol EXAMPLE 4 Dichloro (a-methyl-butyl) ortho-cresol 45 o1 OH "ona-on -cm-on c1 5 This com'pouiidis prepared bythe method of Example 1 except that 58 grams of sulfuryl chloride are used. The product boils at 142-145 C. at 10 mm. pressure and has a specific gravity of 1.116. It is a deep yellow oil, soluble in organic solvents and dilute alkali, insoluble in water.

EXAMPLE 5 Dichloro (a-methyl-butyl) meta-cresol This compound is prepared the same as in EX- ample 4 except for the substitution of (or-methylbutyl) meta cresol. It has a boiling point of 153-158 C. at 9 mm. pressure and has a specific gravity of 1.162. It is an orange colored oil, soluble in dilute alkali and organic solvents, insoluble in water.

EXAMPLE 6 Dichloro (a-methyl-butyl) para-cresol CH-CHr-CHrCH: I 83H: OH

This compound is prepared as in Example 4, substituting (a-methyl-butyl) para-cresol. It has a boiling point of l55160 C. at mm. pressure and has a specific gravity of 1.169. It is an amber colored oil, insoluble in water, soluble in dilute alkali, and organic solvents.

EXAMPLE '7 Monobromo (cc-filthZ/l-b'tbtl/Z) ortho-cresol $13;

18 grams of (u-methyl-butyl) ortho-cresol are dissolved in 50 cc. of chloroform in a flask fitted with a dropping funnel and a reflux condenser. To this is added a little iron powder and then through the funnel is gradually added 16 grams of bromine dissolved in cc. of chloroform. It may be necessary to warm the mixture on a water bath to start the reaction. After all the bromine solution is added, the mixture is warmed for one hour. The mixture is then poured into 200 cc. water and the chloroform layer washed with water. We then separate and distill ofi the chloroform. The residue is dissolved in 200 cc. of normal sodium hydroxide solution and the insoluble portion extracted with petroleum ether.

The clear alkaline portion is acidified and the separated oil is extracted with ether. The ether solution is dried over sodium sulfate and filered; the ether is distilled ofi and the residue distilled under vacuum. It boils at 140--142 0. at 5 mm. pressure and has a specific gravity of soluble in dilute alkali and organic solvents.

This compound is prepared as in the previous example, substituting (cc-IiiGthYl-blltYl) metacresol. It has a boiling point of 152-160 C. at 10 mm. pressure and has a specific gravity of 1.285. It: is a pale yellow oil, insoluble in water, soluble in organic solvents and dilute alkali.

EXAMPLE 9 Monobromo (a-methyl-butyl) para-cresol Br- H-CHz-CHa-CH;

This compound is prepared as in Example 7, substituting (a-methyl-butyl) para-cresol. It boils at 149-152 C. at 10 mm. pressure and has a specific gravity of 1.243. It is a pale yellow oil, soluble in organic solvents and dilute alkali, insoluble in water.

EXAMPLE 10 Dzbromo (u-methyl-butyl) oTtho-cresol CHa The dibromo compounds are prepared by the method of Examples 7-9 except that the quantity of bromine is 38 grams and the quantity of solvent therefor is proportionately increased.

The above product has a boiling point of 175- 176 'C. at 1 2 mm. pressure and has a specific gravity of 1.455. It is an amber colored oil, insoluble in water, soluble in organic solvents and dilute alkali.

v EXAMPLE 11 Dibromo (u-methyZ-butyl) meta-cresol CHa-GHz-OH:CH

This compound boils at 184-188 C. at 9 mm. pressure and has a specific gravity of 1.631. It is a deep yellow oil, insoluble in water, soluble in organic solvents and dilute alkali.

EXAMPLE 12 Dibromo (m-methyl-butyl) para-cresol Br CHCHr-CH:-CH3

compound boils at 165-1'73 C. at 9 mm. pressure and has a specific gravity of 1.547. It is an amber colored oil, insoluble in water, soluble in organic solvents and dilute alkali.

Other halogen derivatives as, for example, iodine compounds of the a-methyl-butyl 'cresols may be similarly prepared and have analogous properties.

The physical properties of the compounds specified above are summarized as follows:

Pres- Compound 13. P. sure Sp. gr.

Degrees centigrade mm. Monochloro (a-methyl-butyl) ortho-cresol 142-150 10 1. 059 Monochloro (a-methyl-butyl) meta-cresol. 145-150 15 1. 142 Monochloro (a-methyl-butyl) para-cresol. 130-134 6 1.050

Dichloro (a-methyl-butyl) ortho-cresol. 142-145 10 l. 116 Dichloro (a-methyl-butyl) meta-cresol 153-158 9 1. 162 Dichloro (a-methyl-butyl) para-cresol" -160 10 1. 169

Monobromo (a-methyl-butyh ortho-cresol 140-142 5 1. 247 Monobromo (a-methyl-butyl) meta-cresol 152-160 10 1. 285 Monobromo (a-methyl-butyl) para-cresol- 148-152 10 1. 243

Dibromo (a-methyl-butyl) ortho-cresol.-- 175-176 12 1.455 Dibromo (a-methyl-butyl) meta-cresoL..- 184-188 9 1. 631 Dibromo (m-methyl-butyl) para-cresoL... -173 9 1. 547

We claim as our invention: 1. A compound having the formula:

R CH (CH1) CHaCHzCH:

wherein R is a cresol nucleus, Y is a halogen, and n is 1 or 2.

2. A compound having the formula R CH (CH3) CHzCHaCHz wherein R. is a cresol nucleus and n is 1 or 2.

3. An a-methyl-butyl cresol which is monohalogenated on the ring.

4. A ring halogenated compound, namely, monochloro (or-methyl-butyl) orthocresol.

5. A ring halogenated compound, namely, monochloro (a-methyl-butyl) paracresol.

6. A ring halogenated compound, namely, monobromo (a-methyl-butyl) metacresol.

GEORGE W. RAIZISS. LE ROY W. CLEMENCE. 

